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    Compositions and methods for modulating the activity of G protein-coupled receptor kinases GPK5 and GRK6
    5.
    发明授权
    Compositions and methods for modulating the activity of G protein-coupled receptor kinases GPK5 and GRK6 失效
    用于调节G蛋白偶联受体激酶GPK5和GRK6的活性的组合物和方法

    公开(公告)号：US06255069B1

    公开(公告)日：2001-07-03

    申请号：US08464954

    申请日：1995-06-06

    申请人： Jeffrey L. Benovic ,  Jorge Gomez ,  Priya Kunapuli

    发明人： Jeffrey L. Benovic ,  Jorge Gomez ,  Priya Kunapuli

    IPC分类号： C12N1512

    CPC分类号： C12N9/1205 ,  C12N2799/026

    摘要： G protein-coupled receptor kinases (GRK) play an important role in phosphorylating and regulating the activity of G protein-coupled receptors. Complementary DNAs (cDNAs) that encode two novel members of the G protein-coupled receptor kinase (GRK) family are provided in the present invention. These cDNAs encode GRK5 (590 amino acids) and GRK6 (576 amino acids) which represent two new members of the GRK family that have distinct tissue distribution and substrate specificity. The availability of the cDNAs enables the generation of reagents to modulate the activity of endogenous kinases. These include dominant negative mutations and antisense oligonucleotides or stably transfected antisense constructs to block expression of the kinase to generate a cell with a reduced ability to desensitize to various agents. Expression of GRK5 and GRK6 also permits identification of specific inhibitors and activators of these two kinases. Such inhibitors and activators may be used therapeutically to either directly modulate the activity of a given receptor or by augmenting the ability of a given therapeutic agent to stimulate a given receptor.

    摘要翻译： G蛋白偶联受体激酶（GRK）在磷酸化和调节G蛋白偶联受体的活性中起重要作用。 在本发明中提供了编码G蛋白偶联受体激酶（GRK）家族的两个新成员的互补DNA（cDNA）。 这些cDNA编码GRK5（590个氨基酸）和GRK6（576个氨基酸），其代表具有不同组织分布和底物特异性的GRK家族的两个新成员。 cDNA的可用性使得能够产生用于调节内源性激酶活性的试剂。 这些包括显性阴性突变和反义寡核苷酸或稳定转染的反义构建体以阻断激酶的表达以产生具有降低对各种试剂的敏感能力的细胞。 GRK5和GRK6的表达还可以鉴定这两种激酶的特异性抑制剂和活化剂。 这样的抑制剂和活化剂可以用于治疗性地直接调节给定受体的活性或增加给定治疗剂刺激给定受体的能力。

    Method of detecting inhibitors of agonist-specific desensitization
    6.
    发明授权
    Method of detecting inhibitors of agonist-specific desensitization 失效
    检测激动剂特异性脱敏抑制剂的方法

    公开(公告)号：US06605424B1

    公开(公告)日：2003-08-12

    申请号：US09568983

    申请日：2000-05-11

    申请人： Robert J. Lefkowitz ,  Martin J. Lohse ,  Jeffrey L. Benovic ,  Marc G. Caron

    发明人： Robert J. Lefkowitz ,  Martin J. Lohse ,  Jeffrey L. Benovic ,  Marc G. Caron

    IPC分类号： C12Q300

    CPC分类号： A61K31/715 ,  A61K31/21 ,  A61K31/66 ,  A61K31/675 ,  A61K38/1787 ,  G01N33/566 ,  G01N33/573

    摘要： The present invention relates to a method of inhibiting desensitization of a cell to the effects of a compound. The method comprises contacting the cell with an agent capable of inhibiting phosphorylation, by a protein kinase, of a receptor for the compound present on the surface of the cell. The present invention also relates to a method of screening a compound for its ability to inhibit desensitization. The method comprises: i) contacting a receptor specific kinase-containing sample with the compound under conditions such that interaction between receptor specific kinase present in the sample and the compound can occur, and ii) determining the ability of the receptor specific kinase to phosphorylate the receptor for which it is specific.

    摘要翻译： 本发明涉及抑制细胞对化合物作用的脱敏的方法。 该方法包括使细胞与能够通过蛋白激酶抑制存在于细胞表面的化合物的受体的磷酸化的试剂接触。 本发明还涉及一种筛选化合物抑制脱敏能力的方法。 该方法包括：i）使受体特异性激酶样品与化合物在使得存在于样品中的受体特异性激酶与化合物之间发生相互作用的条件下接触，以及ii）确定受体特异性激酶使受体磷酸化的能力 它是具体的。